Guodong Xiao1, Yuan Li2, Meng Wang1, Xiang Li1, Sida Qin1, Xin Sun1, Rui Liang3, Boxiang Zhang1, Ning Du1, Chongwen Xu4, Hong Ren1, Dapeng Liu1. 1. Department of Thoracic Surgery and Oncology, The Second Department of Thoracic Surgery, Cancer Center, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China. 2. School of Humanities & Social Sciences, Xi'an Jiaotong University, Xi'an, China. 3. Department of Hepatobiliary Chest Surgery, Shaanxi Provincial Corps Hospital of Chinese People's Armed Police Force, Xi'an, China. 4. Department of Otorhinolaryngology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Abstract
OBJECTIVES: FBXW7 acts as a tumour suppressor by targeting at various oncoproteins for ubiquitin-mediated degradation. However, the clinical significance and the involving regulatory mechanisms of FBXW7 manipulation of NSCLC regeneration and therapy response are not clear. MATERIALS AND METHODS: Immunohistochemical staining and qRT-PCR were applied to detect FBXW7 and Snai1 expression in 100 samples of NSCLC and matched tumour-adjacent tissues. FBXW7 manipulation of cancer biological functions were studied by using MTT assay, immunoblotting, flow cytometry, transwells, wound healing assay, and sphere-formation assays. Immunofluorescence and co-immunoprecipitation were used to analyse the possible interaction between Snai1 and FBXW7. RESULTS: We detected the decreased FBXW7 expression in majority of the NSCLC tissues, and lower FBXW7 level was correlated with advanced TNM stage. Furthermore, those patients with decreased FBXW7 expression tend to have both poorer 5-year survival outcomes, and shorter disease-free survival, comparing to those with higher FBXW7 levels. Functionally, we found that FBXW7 enforcement suppressed NSCLC progression by inducing cell growth arrest, increasing chemo-sensitivity and inhibiting Epithelial-mesenchymal Transition (EMT) progress. Results further showed that FBXW7 could interact with Snai1 directly to degrade its expression through ubiquitylating alternation in NSCLC, which could be partially abrogated by restoring Snai1 expression. CONCLUSIONS: FBXW7 conduction of tumour suppression was partly through degrading Snai1 directly for ubiquitylating regulation in NSCLC.
OBJECTIVES:FBXW7 acts as a tumour suppressor by targeting at various oncoproteins for ubiquitin-mediated degradation. However, the clinical significance and the involving regulatory mechanisms of FBXW7 manipulation of NSCLC regeneration and therapy response are not clear. MATERIALS AND METHODS: Immunohistochemical staining and qRT-PCR were applied to detect FBXW7 and Snai1 expression in 100 samples of NSCLC and matched tumour-adjacent tissues. FBXW7 manipulation of cancer biological functions were studied by using MTT assay, immunoblotting, flow cytometry, transwells, wound healing assay, and sphere-formation assays. Immunofluorescence and co-immunoprecipitation were used to analyse the possible interaction between Snai1 and FBXW7. RESULTS: We detected the decreased FBXW7 expression in majority of the NSCLC tissues, and lower FBXW7 level was correlated with advanced TNM stage. Furthermore, those patients with decreased FBXW7 expression tend to have both poorer 5-year survival outcomes, and shorter disease-free survival, comparing to those with higher FBXW7 levels. Functionally, we found that FBXW7 enforcement suppressed NSCLC progression by inducing cell growth arrest, increasing chemo-sensitivity and inhibiting Epithelial-mesenchymal Transition (EMT) progress. Results further showed that FBXW7 could interact with Snai1 directly to degrade its expression through ubiquitylating alternation in NSCLC, which could be partially abrogated by restoring Snai1 expression. CONCLUSIONS:FBXW7 conduction of tumour suppression was partly through degrading Snai1 directly for ubiquitylating regulation in NSCLC.